DEVELOPMENT AND CHARACTIZATION OF EFFECTIVE HEPATITIS C VIRUS NEUTRALIZING ANTIBODIES

Shiri Elmedvi Baran ¹ Ateret Davidovich ¹ Sivan Eliyahu ¹ Yoav Bahat ¹ Marius Braun ² Larisa Bachmatov ³ Romy Zemel ³ Assy Nimer ⁴ Michal Carmiel-Hagai ⁵ Shifra Sela ^4,5 Meital Gal-Tanamy ¹

¹Molecular Virology Lab, Faculty of Medicine in the Galilee, Bar-Ilan University, Zafed
²Liver Institute, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv
³Molecular Hepatology Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv
⁴., Western Galilee Hospital, Naharyia
⁵Eliachar Research Laboratory, Western Galilee Hospital, Naharyia

Aim & Background: Hepatitis C virus (HCV) is a major public health problem worldwide. There are 200 million people that are chronically infected and at risk for developing life-threatening liver disease. There is a critical gap in understanding HCV immunity. We hypothesize that spontaneously cleared (SC) patients, may possess higher levels of HCV-specific B-cell immunity, comparing to chronically infected (CI) subjects. We studied the nature of successful immune response against HCV and developed effective HCV-neutralizing antibodies.

Methods: Sera and B cells were collected from CI and SC patients. Sera used us for neutralization assays and B cells for constructing two antibodies libraries (CI and SC’s libraries) using phage display technology. Specific binding and neutralizing antibodies were isolated from those libraries.

Results& Conclusion: We have observed high titer of HCV-specific antibodies in the sera of CI patients compared to low levels of antibodies in the sera of SC`s. In contrast, high levels of HCV neutralization were observed with SC`s sera. Following five rounds of panning, we have isolated a panel of unique antibodies form each antibody libraries. These antibodies exhibited specify for HCV and high ability to neutralize HCV infection.

This study suggests that SC patients exhibit unique and efficient B cells response comparing to CI. The isolation of unique antibodies may open new avenues to effective immunoglobulin-based therapies that could prove helpful in preventing or treating HCV-related liver disease and would benefit vaccine development efforts.